HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Robert E. Stroud Francis G. Spinale Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by McEvoy, M. D. Articles by Spinale, F. G. Search for Related Content PubMed PubMed Citation Articles by McEvoy, M. D. Articles by Spinale, F. G. Related Collections Cardiac - pharmacology

---

Original Articles: Adult Cardiac

Aprotinin Exerts Differential and Dose-Dependent Effects on Myocardial Contractility, Oxidative Stress, and Cytokine Release After Ischemia-Reperfusion

^a Department of Anesthesiology and Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina
^b Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina
^c Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina

Accepted for publication April 9, 2008.

^_* Address correspondence to Dr Spinale, Division of Cardiothoracic Surgery, Medical University of South Carolina, 114 Doughty St, Rm 625, Charleston, SC 29403 (Email: wilburnm{at}musc.edu).

Background: Cardiac surgery can result in left ventricular ischemia and reperfusion (I/R), the release of cytokines such as tumor necrosis factor, and oxidative stress with release of myeloperoxidase. Although aprotinin has been used in cardiac surgery, the likely multiple effects of this serine protease inhibitor limit clinical utility. This study tested the hypothesis that different aprotinin doses cause divergent effects on left ventricular contractility, cytokine release, and oxidative stress in the context of I/R.

Methods: Left ventricular I/R (30 minutes I, 60 minutes R) was induced in mice, and left ventricular contractility (maximal end-systolic elastance) determined. Mice were randomly allocated to 2 x 10⁴ kallikrein inhibitory units (KIU)/kg aprotinin (n = 11), 4 x 10⁴ KIU/kg aprotinin (n = 10), and vehicle (saline, n = 10). Based upon a fluorogenic assay, aprotinin doses of 2 and 4 x 10⁴ KIU/kg resulted in plasma concentrations similar to those of the half and full Hammersmith doses, respectively.

Results: After I/R, maximal end-systolic elastance fell by more than 40% from baseline (p < 0.05), and this effect was attenuated by 2 x 10⁴ KIU/kg but not 4 x 10⁴ KIU/kg aprotinin. Tumor necrosis factor increased by more than 60% from control (p < 0.05) with I/R, but was reduced with 4 x 10⁴ KIU/kg aprotinin. Myeloperoxidase increased with I/R, and was reduced to the greatest degree by 2 x 10⁴ KIU/kg aprotinin.

Conclusions: Aprotinin influences left ventricular contractility, cytokine release, and oxidative stress, which are dose dependent. These results provide mechanistic evidence that multiple pathways are differentially affected by aprotinin in a context relevant to cardiac surgery.